Methods: The synthesized formulation was characterized using FT-IR and LC-MS along with organoleptic evaluation. Thereafter neuroprotective efficacy of BNC formulation was subsequently investigated against Diclofenac-induced oxidative stress in SH-SY5Y cells. The cells were pretreated with synthesized formulation and subsequently evaluated for amelioration in Diclofenac-induced cytotoxicity, and ROS augmentation. The neuroprotective effect of synthesized formulation was further explored by evaluating the changes in nuclear morphology, and apoptosis alleviation with concomitant regulatory effects on caspase-3 and -9 activation.

Results: Diclofenac was found to be considerably cytotoxic against human neuroblastoma SHSY5Y cells. Intriguingly, Diclofenac-mediated toxicity was reduced significantly in SH-SY5Y cells pretreated with BNC formulation. Augmented ROS levels within Diclofenac-treated SHSY5Y cells were also reduced in the BNC formulation pretreated SH-SY5Y cells. Furthermore, BNC formulation pretreated SH-SY5Y cells also exhibited reduced dissipation of mitochondrial membrane potential, caspase-3 and -9, along with apoptosis after Diclofenac treatment.

Conclusion: These findings indicated that, indeed, Diclofenac induces considerable ROSmediated apoptosis in SH-SY5Y cells, which further intriguingly ameliorated Diclofenacmediated cytotoxic effects on SH-SY5Y cells. This manuscript further collected information about available National and International patents published or granted in preparation of and thereof applications against motor and non-motor brain dysfunctions.

Objectives: The objective of this study is to investigate the effects of RBM3 on skin wound healing in diabetes.

Methods: In vitro experiments, western blot assay was used to test the levels of proteins in HaCaT cells treated with different concentrations of glucose. RBM3 was over-expressed in HaCaT cells using lentivirus particles. Cell viability was analyzed by Cell-Counting Kit-8 assay and colony formation assay. The migration of HaCaT cells at different concentrations of glucose was evaluated by wound healing assay. In vivo experiments, the mouse model of diabetes was established by intraperitoneal injection of streptozotocin. Four weeks later, the mice were anesthetized by intraperitoneal injection of pentobarbital sodium for skin tissue collection or wound healing experiments. RBM3 knockout mice were established by removing exons 2–6 using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technique and then used in skin wound healing experiments with or without diabetic stress.

Results: In this study, the expression of RBM3, rather than CIRP, was altered in the skin of diabetic specimens, and the RBM3’s overexpression accelerated the cell viability and proliferation of HaCaT cells under high glucose conditions. RBM3 deficiency caused delayed wound healing in RBM3 knockout in diabetic conditions. Moreover. RBM3 enhanced the ERK1/2 signaling pathway, and its inhibitor FR180204 blocked the beneficial effect of RBM3 overexpression on skin wound healing in diabetes.

Conclusion: RBM3 activated the ERK1/2 signal to facilitate skin wound healing in diabetes, offering a novel therapeutic target for its treatment.

Background: GBM is the most malignant primary brain cancer with a poor prognosis. Previous studies have suggested that GBM vessels undergo dynamic remodeling modulated by tumor vasodilation and vasoconstriction instead of tumor angiogenesis.

Objective: Here, we have first investigated the expression and function of UTS2, a potent vasoconstrictor, in GBM.

Methods: The mRNA expression profiles and clinical information of GBM patients were obtained from the TCGA database. The clinical relevance of UTS2 was explored by the Mann-Whitney U test and Cox hazard regression survival test. We further explored the role of UTS2 in GBM cell proliferation, migration, and tumor immune microenvironment. Moreover, we established the in vivo mice model to validate its oncogenic effects on GBM progression.

Results: Although we did not find significant correlations between UTS2 expression and patients’ clinical characteristics, UTS2 was identified as a valid independent prognostic indicator according to multivariate survival analysis. Knockdown of UTS2 resulted in decreased GBM cell proliferation and migration. In addition, functional enrichment analysis implied UTS2 to be involved in the regulation of the immune microenvironment. In vivo studies showed that UTS2 knockdown suppressed GBM xenograft growth, highlighting the tumor-promoting effects of UTS2 on GBM.

Conclusion: Our study identified that UTS2 could predict the prognosis of GBM patients and provided evidence regarding its oncogenic effects both in vitro and in vivo.

Methods: In this work, expression differences of ADGRL4 in human NB cell lines and HUVECs were assessed via RT-qPCR and western blot analysis. For functional experiments, sh-ADGRL4 was transfected into SK-N-SH cells to generate ADGRL4 knockdown stable cell line. Moreover, ADGRL4 knockdown stable SK-N-SH cells were treated with LM22B-10 (an ERK activator) for rescue experiments. CCK-8, colony formation, would healing, and transwell assays determined NB cell growth, migration, and invasion. Meanwhile, proliferation-, metastasis- and EMT- associated proteins were also detected. Additionally, a tube formation assay was employed to evaluate in vitro angiogenesis. VM-cadherin, the marker of angiogenesis, was assessed using immunofluorescence staining.

Results: Data showed notably upregulated ADGRL4 in NB cells, especially in SK-NSH cells. ADGRL4 knockdown inhibited NB cell growth, migration, invasion, EMT, and in vitro angiogenesis. ADGRL4 knockdown inactivated ERK/STAT3 signaling pathway. Activation of the ERK/STAT3 signaling pathway partially rescued the tumor suppression effects of ADGRL4 knockdown on NB cells.

Conclusion: To conclude, the downregulation of ADGRL4 may inhibit cell growth, aggressiveness, EMT, and angiogenesis in NB by inactivating the ERK/STAT3 signaling pathway.

Objective: The objective of this article is to investigate the potential of herbal medications as a treatment option for Parkinsonism, and to provide a clear understanding of the current state of research on this topic.

Conclusion: This review focuses on herbal treatments and components that have demonstrated promise in Parkinson's disease in vitro and animal models. This information can be used to identify prospective traditional medicine prescription therapies. New therapeutic treatments for Parkinson's disease may result from further study of pharmaceutical components with well-established therapeutic potential.

Case Presentation: We have, herein, presented a case with stage IV neuroblastoma who relapsed after 11 years and had a subsequent relapse after 15 years from the initial diagnosis, and reviewed cases with late relapsed (after >5 years) neuroblastoma in the literature. The case presented with recurrent disease at the T7 vertebra after 11 years from the initial diagnosis. The patient received surgery, che motherapy, MIBG treatment, and antiGD2 combined with che motherapy, and had a further local recurrence in the paravertebral area of the re moved T7 vertebra after three years. The patient was operated, received anti-GD2 combined with che motherapy, and is still alive with no symptoms for 19 months after the last relapse.

Conclusion: There is not a well-established treatment regimen for the majority of these patients. MIBG treatment and antiGD2 combined with che motherapy may be promising options for relapsed/ refractory neuroblastoma.

Methods: To investigate the role of NNAT, its expression was silenced in NSCLC cell lines A549 and H226. Subsequently, various parameters, including cell proliferation, invasion, migration, and apoptosis, were assessed. Additionally, cell-derived xenograft models were established to evaluate the effect of NNAT knockdown on tumor growth. The expression of key molecules, including cyclin D1, B-cell leukemia/lymphoma 2 (Bcl-2), p65, matrix metalloproteinase (MMP) 2, and nerve growth factor (NGF) were examined both in vitro and in vivo. Nerve fiber density within tumor tissues was analyzed using silver staining.

Results: Upon NNAT knockdown, a remarkable reduction in NSCLC cell proliferation, invasion, and migration was observed, accompanied by elevated levels of apoptosis. Furthermore, the expression of cyclin D1, Bcl-2, MMP2, and phosphorylated p65 (p-p65) showed significant downregulation. In vivo, NNAT knockdown led to substantial inhibition of tumor growth and a concurrent decrease in cyclinD1, Bcl-2, MMP2, and p-p65 expression within tumor tissues. Importantly, NNAT knockdown also led to a decrease in nerve fiber density and downregulation of NGF expression within the xenograft tumor tissues.

Conclusion: Collectively, these findings suggest that neuronatin plays a pivotal role in driving NSCLC progression, potentially through the activation of the nuclear factor-kappa B signaling cascade. Additionally, neuronatin may contribute to the modulation of tumor microenvironment innervation in NSCLC. Targeting neuronatin inhibition emerges as a promising strategy for potential anti-NSCLC therapeutic intervention.

Objective: The aim of this study was to explore the binding affinity of natural molecules derived from G. biloba to essential biomarkers associated with CRC, including Kirsten rat sarcoma virus, neuroblastoma RAS mutations, serine/threonine-protein kinase B-Raf, phosphatidylinositol 3'-kinase, and deleted colorectal cancer, using molecular docking. The focus of this research was to evaluate how effectively these molecules bind to specified targets in order to identify potential inhibitors for the treatment of CRC.

Methods: A total of 152 polyphenolic compounds from G. biloba were selected and subjected to molecular docking simulations to evaluate their interactions with CRC-related biomarkers. The docking results were analysed to identify ligands exhibiting strong affinities towards the targeted genes, suggesting potential inhibitory effects.

Results: Docking simulations unveiled the strong binding affinities between selected polyphenolic compounds derived from G. biloba and genes associated with CRC. The complex glycoside structures that are found in flavonols are of significant importance. These compounds, including derivatives with distinctive arrangements, exhibited promising docking scores, signifying substantial interactions with the targeted biomarkers.

Conclusion: The study demonstrates the potential of G. biloba-derived molecules as effective anticancer agents for colorectal cancer. The identified ligands exhibit strong interactions with crucial CRC-related biomarkers, suggesting potential inhibition ability. Further in vitro and in vivo investigations are needed to validate and build upon these promising findings, advancing the development of novel and efficient CRC therapies.

Background: High expression and activity of the lipoxygenase enzyme (LOX) have been detected in several tumors, including neuroblastoma samples, suggesting the use of LOX inhibitors as potential therapy molecules. Among these, the natural compound nordihydroguaiaretic acid (NDGA) has been extensively tested as an antiproliferative drug against diverse types of cancer cells.

Objective: In this study, we analyzed the toxic effect of NDGA on neuroblastoma cells at a dose that did not affect cell survival when they differentiated to a neuron-like phenotype and the potential mechanisms involved in the anticancer properties.

Methods: We exposed human neuroblastoma cells (MSN) to different concentrations of NDGA before and after a differentiation protocol with retinoic acid and nerve growth factor and analyzed cell viability, cell migration, actin cytoskeleton morphology and the levels of the cell cycle inhibitor p21^WAF1/CIP1 and 5-LOX.

Results: We found that differentiated human neuroblastoma cells are more resistant to NDGA than undifferentiated cells. The toxic effects of NDGA were accompanied by reduced cell migration, changes in actin cytoskeleton morphology, induction of p21^WAF1/CIP1 and decreased levels of the 5-LOX enzyme.

Conclusion: This study provides new evidence regarding the potential use of NDGA to induce cell death in human neuroblastoma.

Objective: This comprehensive review was aimed to critically explore diverse pharmacological activities exhibited by diosmetin. Along with that, this review can also identify potential research areas with an elucidation of the multifactorial underlying signaling mechanism of action of diosmetin in different diseases.

Methods: A comprehensive collection of evidence and insights was obtained from scientific journals and books from physical libraries and electronic platforms like Google Scholar and PubMed. The time frame selected was from year 1992 to July 2023.

Results: The review delves into diosmetin's impact on cellular signaling pathways and its potential in various diseases. Due to its ability to modulate signaling pathways and reduce oxidative stress, it can be suggested as a potential versatile therapeutic agent for mitigating oxidative stressassociated pathogenesis.

Conclusion: The amalgamation of the review underscores diosmetin's promising role as a multifaceted therapeutic agent, highlighting its potential for drug development and clinical applications.

Objectives: The purpose of this article is to familiarize physicians with the clinical manifestations of premature thelarche and laboratory tests that may help distinguish premature thelarche from central precocious puberty.

Methods: A search was conducted in September 2022 in PubMed Clinical Queries using the key term \"Premature thelarche\". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used to compile the present article.

Results: Premature thelarche denotes isolated breast development before the age of 8 years in girls who do not manifest other signs of pubertal development. The condition is especially prevalent during the first two years of life. The majority of cases of premature thelarche are idiopathic. The condition may result from an unsuppressed hypothalamic-pituitary-gonadal axis in the early years of life, an \"overactivation\" of the hypothalamic-pituitary axis in early childhood secondary to altered sensitivity to steroids of the hypothalamic receptors controlling sexual maturation, increased circulating free estradiol, increased sensitivity of breast tissue to estrogens, and exposure to exogenous estrogens. The cardinal feature of premature thelarche is breast development which occurs without additional signs of pubertal development in girls under 8 years of age. The enlargement may involve only one breast, both breasts asymmetrically, or both breasts symmetrically. The breast size may fluctuate cyclically. The enlarged breast tissue may be transiently tender. There should be no significant changes in the nipples or areolae and no pubic or axillary hair. The vulva, labia majora, labia minora, and vagina remain prepubertal. Affected girls have a childlike body habitus and do not have mature contours. They are of average height and weight. Growth and osseous maturation, the onset of puberty and menarche, and the pattern of adolescent sexual development remain normal. Most cases of premature thelarche can be diagnosed on clinical grounds. Laboratory tests are seldom indicated. No single test can reliably differentiate premature thelarche from precocious puberty.

Conclusion: Premature thelarche is benign, and no therapy is necessary apart from parental reassurance. As enlargement of breasts may be the first sign of central precocious puberty, a prolonged follow- up period every 3 to 6 months with close monitoring of other pubertal events and linear growth is indicated in all instances.

This review summarises the current concepts in pathophysiology, the clinical features that help differentiate important differential diagnoses, and an approach to investigating and managing children with CNO. Ultimately, the timely and thorough investigation of children and young people with CNO is vitally important to exclude important mimics and initiate appropriate management that can prevent the complications of persistent inflammatory bone disease.

Methods: We used Gene Expression Omnibus for target gene identification, while KEGG was used to delineate CC-related pathways. Proliferation, migration, and apoptosis levels in CC cells were assessed using CCK8, Transwell, and flow cytometry, respectively. The effect of the target genes on the in vivo tumorigenesis of CC cells was evaluated using the subcutaneous tumorigenesis assay.

Results: ZIP14 (SLC39A14) was found to be underexpressed in CC samples. Our KEGG pathway analysis revealed the potential involvement of the P38 mitogen-activated protein kinase (MAPK) pathway in CC pathogenesis. Overexpression of ZIP14 in HeLa and Caski cells increased p38 phosphorylation, inhibited cell growth and migration, and enhanced apoptosis. Conversely, ZIP14 knockdown produced the opposite effects. Importantly, the bioeffects induced by ZIP14 overexpression could be counteracted by the p38 MAPK pathway inhibitor SB203580. In vivo experiments further confirmed the influence of ZIP14 on CC cell migration.

Conclusion: Our study is the first to elucidate the pivotal role of ZIP14 in the pathogenesis of CC, revealing its inhibitory effects through the activation of the p38 MAPK signaling pathway. The discovery not only provides a deeper understanding of CC's molecular underpinnings, but also highlights ZIP14 as a promising therapeutic target. As ZIP14 holds significant potential for therapeutic interventions, our findings lay a robust foundation for further studies and pave the way for the exploration of novel treatment modalities for cervical cancer.

Methods: A novel, practical and efficient three-component synthesis of cycloalkane-fused pyrazolo[ 4,3-e]pyridines was developed through a tandem reaction of 5-aminopyrazoles, cyclic ketones and electron-rich olefins, using microwave induction in perfluorinated solvent and iodine as catalyst.

Results: The microwave-induced three-component approach applied in this work promoted the construction of 10 new pyrazolopyridines with high speed and excellent control of regioselectivity, favoring the linear product with good yields; where the versatility of electron-rich olefins in iodine-catalyzed cascade heterocyclizations, granted the additional benefit of easy isolation and the possibility to reuse the fluorous phase.

Conclusion: Although pyrazolopyridines have been synthetically explored because of their structural and biological properties, most of the reported synthetic methods use common or even toxic organic solvents and conventional heating or multi-step processes. In contrast, this study applied a multicomponent methodology in a single step by microwave induction and with the versatility provided in this case by the use of perfluorinated solvent, which allowed easy isolation of the final product and recovery of the fluorous phase.

Objective: This review focused on the compilation of promising data from thiazole, isatin, and phthalimide derivatives, reported in the literature between 2015 and 2022, with in vivo anticancer activity and clinical trials.

Methods: A bibliographic search was carried out in the PUBMED, MEDLINE, ELSEVIER, and CAPES PERIODIC databases, selecting relevant works for each pharmacophoric group with in vivo antitumor activity in the last 6 years.

Results: In our study, 68 articles that fit the scope were selected and critically analyzed. These articles were organized considering the type of antitumor activity and their year of publication. Some compounds reported here demonstrated potent antitumor activity against several tumor types.

Conclusion: This review allowed us to highlight works that reported promising structures for the treatment of various cancer types and also demonstrated that the privileged structures thiazole, isatin and phthalimide are important in the design of new syntheses and molecular optimization of compounds with antitumor activity.

Objective: We intend to purport the suitably engineered cobalt sulfide and dysprosium-doped cobalt sulfide nanoparticles that are magnetic and NIR-absorbing, as drug delivery vehicles. The drug loading and release are based on the supramolecular drug complex formation on the surface of the nanoparticles.

Method: The nanomaterials are synthesized employing hydrothermal procedures, coated with a biocompatible poly-β-cyclodextrin, and characterized using the methods of diffractometry, microscopy, spectroscopy, thermogravimetry and magnetometry. The sustained drug release is investigated in vitro. 5-Fluorouracil is loaded in the nanocarriers. The empty and 5-fluorouracil-loaded nanocarriers are screened for their anti-breast cancer activity in vitro on MCF-7 cells.

Results: The size of the nanoparticles is below 10 nm. They show soft ferromagnetic characteristics. Further, they show broad NIR absorption bands extending up to 1200 nm, with the dysprosium-doped material displaying greater absorbance. The drug 5-fluorouracil is encapsulated in the nanocarriers and released sustainably, with the expulsion duration extending over 10 days. The IC₅₀ of the blank and the drug-loaded cobalt sulfide are 16.24 ± 3.6 and 12.2 ± 2.6 μg mL^-1, respectively. For the drug-loaded, dysprosium-doped nanocarrier, the IC₅₀ value is 9.7 ± 0.3 μg mL^-1.

Conclusion: The ultrasmall nanoparticles possess a size suitable for drug delivery and are dispersed well in the aqueous medium. The release of the loaded 5-fluorouracil is slow and sustained. The anticancer activity of the drug-loaded nanocarrier shows an increase in efficacy, and the cytotoxicity is appreciable due to the controlled release. The nanocarriers show multi-functional characteristics, i.e., magnetic and NIR-absorbing, and are promising drug delivery agents.

Objective: In this study, a tumor-targeting LIV-1 VHH-mutIL2 immunocytokine with reduced CD25 (α chain of the high-affinity IL-2 receptor) binding activity was developed to improve IL-2 half-life by decreasing its renal infiltration in comparison with wild and mutant IL-2 molecules.

Methods: The recombinant immunocytokine was designed and expressed. The biological activity of the purified fusion protein was investigated in in vitro and in vivo experiments.

Results: The fusion protein represented specific binding to MCF7 (the breast cancer cell line) and more efficient cytotoxicity than wild-type IL-2 and mutant IL-2. The PK parameters of the recombinant immunocytokine were also improved in comparison to the IL-2 molecules.

Conclusion: The observed results showed that LIV1-mIL2 immunocytokine could be considered as an effective agent in the LIV-1-targeted treatment of cancers due to its longer half-life and stronger cytotoxicity.

Objective: The current study aims to determine the efficacy of CYN against BPA-induced neuropathology.

Methods: In vitro experiments utilized PC12 cells were pre-treated with gradient doses of CYN and further stimulated with 10ng/ml of BPA. DPPH radical scavenging activity, catalase activity, total ROS activity, and nitric oxide radical scavenging activity were done. In vivo assessments employed doublecortin immunohistochemistry of the brain in BPA-exposed Sprague-Dawley rats. Further, In silico molecular docking of CYN with all proteins involved in canonical Wnt signaling was performed using the Autodock v4.2 tool and BIOVIA Discovery Studio Visualizer.

Results: IC₅₀ values of CYN and ascorbic acid were determined using dose-response curves, and it was found to be 24.68 ± 0.563 μg/ml and 20.69 ± 1.591μg/ml, respectively. BPA-stimulated cells pre-treated with CYN showed comparable catalase activity with cells pre-treated with ascorbic acid (p = 0.0287). The reactive species production by CYN-treated cells was significantly decreased compared to BPA-stimulated cells (p <0.0001). Moreover, CYN significantly inhibited nitric oxide production compared to BPA stimulated and the control cells (p < 0.0001). In vivo CYN positively affected immature neuron quantity, correlating with dosage. During molecular docking analysis, CYN exhibited a binding affinity > -7 Kcal/mol with all the key proteins associated with the Wnt/β- catenin signaling cascade.

Conclusion: Conclusively, our finding suggests that CYN exhibited promise in counteracting BPAinduced oxidative stress, improving compromised neurogenesis in hippocampal and cortical regions, and displaying notable interactions with Wnt signaling proteins. Thereby, CYN could render its neuroprotective potential against BPA-induced neuropathology.

Methods: ZNS was labeled with ^99mTc and the radiochemical yield of [^99mTc]Tc-ZNS was determined with TLRC (Thin Layer Liquid Radio Chromatography and HPLRC (High Performance Liquid Radio Chromatography) radiochromatographic methods. In vitro behavior of [^99mTc]Tc-ZNS was determined with time-dependent uptake of [^99mTc]Tc-ZNS on the SHSY5Y human neuroblastoma cells.

Results: The radiochemical yield of [^99mTc]Tc-ZNS was determined as 98.03 ± 1.24% (n = 6) according to radiochromatographic studies results. [^99mTc]Tc-ZNS demonstrated 5.38 and 6.18 times higher uptake values than the control group on the human neuroblastoma SH-SY5Y cell line at 120 and 240 minutes, respectively.

Conclusion: This study showed that the current radiolabeled antiepileptic drug has a diagnostic potential to be used in imaging neurological processes.

]]> https://www.benthamscience.comarticle/137985Erwiniachrysanthemi-derived asparaginase) approved by the U.S. FDA between 2018 to 2021. These drugs act as anticancer agents against various cancer types, especially non-small cell lung, lymphoma, breast, prostate, multiple myeloma, neuroendocrine tumor, cervical, bladder, cholangiocarcinoma, myeloid leukemia, gastrointestinal, neuroblastoma, thyroid, epithelioid and cutaneous squamous cell carcinoma. The review comprises the key structural features, approval times, target selectivity, mechanisms of action, therapeutic indication, formulations, and possible synthetic approaches of these approved drugs. These crucial details will benefit the scientific community for futuristic new developments in this arena.]]> https://www.benthamscience.comarticle/137935 https://www.benthamscience.comarticle/132614 https://www.benthamscience.comarticle/133308Background: Polo-like kinase 1 (PLK1) is an important target for anti-cancer drugs. A series of novel 2,4-diarylaminopyrimidine derivatives (DAPDs) as PLK1 inhibitors (PLKIs) with remarkable activities have been reported recently.

Methods: A systemically computational study was performed on these DAPDs, including threedimensional quantitative structure-activity relationship (3D-QSAR) modeling, molecular docking, and molecular dynamics (MD) simulation.

Results: The constructed 3D-QSAR models exhibited reliable predictability with satisfactory validation parameters. The dockings revealed the binding modes of DAPDs in PLK1 protein, and two key residue, Cys133 and Phe183, could interact with DAPDs by hydrogen bonds and π-π stacking, which might be significant for the activity of these PLKIs. Eight compounds with higher predicted activity than the most active DAPD-compound (16) were designed based on the 3D-QSAR models. These newly designed compounds also exhibited higher docking scores than compound 16 in the binding pocket of PLK1. The ADME predictions and MD simulations further indicated that two hit compounds with reasonable pharmacokinetics properties could stably bind with PLK1 and have the potential to become novel PLKIs.

Conclusion: Two newly designed compounds might have the potential to be novel PLKIs. These results might provide important information for the design and development of novel PLKIs.

Objective: Different coordination complexes have been assessed for their efficacy to target MDR and surpass side effects associated with platinum drugs. In this work, we have prepared and investigated the anticancer potential of new platinum compounds of 3- hydroxy-2-formylpyridine thiosemicarbazones.

Methods: Novel Pt(II) complexes were synthesized and characterized by elemental analyses, FT-IR, ¹H-NMR, UV-visible spectroscopy, and mass spectrometry. The in vitro anticancer activity of the synthesized compounds against HeLa cells by MTT assay was assessed. Protein-fixed and ligand-flexible docking studies were carried out using the Lamarckian genetic algorithm and Autodock 4.2 software.

Results: The IC₅₀ values of compounds (3) and (4) through MTT screening against HeLa cells were found to be 107.16 μM and 132.13 μM, respectively. The binding energy value for the complex [Pt(HyPyMe)Cl] was -6.49 kcal/mol. While for complex, [Pt(HyPyPyrd)Cl] was found to have a binding energy value of -6.83 kcal/mol.

Conclusion: The spectroscopic and analytical data showed the mononuclear structures and square planar geometry of the Pt(II) complexes. The compounds exhibited moderate antineoplastic activity, and N(4)-methyl-substituted compound exhibited better anticancer activity. [Pt(HyPyMe)Cl] complex formed hydrogen bond interactions with guanine-6, guanine-7 and thiamine-8. While, [Pt(HyPyPyrd)Cl] interacted with guanine-7 and guanine-16 via hydrogen bond interaction.

Methods: Palliative treatment options for psoriasis often prioritize the use of volatile oils. These oils contain monoterpenes, sesquiterpenes, and phenylpropanoids that are intricately linked to the molecular cascades involved in the pathogenesis and symptoms of psoriasis. To evaluate the antipsoriatic efficacy of volatile oils and their components, we conducted a systematic review of scientific studies. Our literature search encompassed various online databases, including PubMed, BIREME, SCIELO, Open Grey, Scopus, and ScienceDirect. The selected studies included experimental in vitro/in vivo assessments as well as clinical studies that examined the potential of volatile oils and their extracts as antipsoriatic agents. We excluded conference proceedings, case reports, editorials, and abstracts. Ultimately, we identified and evaluated a total of 12 studies for inclusion in our analysis.

Results: The data collected, compiled, and analyzed strongly support the interaction between volatile oils and their constituents with the key molecular pathways involved in the pathogenesis of psoriasis and the development of its symptoms. Volatile oils play a significant role in the palliative treatment of psoriasis, while their chemical constituents have the potential to reduce the symptoms and recurrence of this condition.

Conclusion: The current review highlights that the constituents found in volatile oils offer distinct chemical frameworks that can be regarded as promising starting points for the exploration and development of innovative antipsoriatic agents.

Objective: This review is carried out to highlight the role of tropomyosin receptor kinase in cancer and the function of TRK inhibitors in the intervention of cancer.

Methods: Literature research has been accomplished using Google Scholar and databases like ScienceDirect, WOS, PubMed, SciFinder, and Scopus.

Results: In this review, we provide an overview of the main molecular and functional properties of TRKs and their inhibitors. It also discusses how these advancements have affected the development and use of novel treatments for malignancies and other conditions caused by activated TRKs. Several therapeutic strategies, including the discovery and development of small-molecule TRK inhibitors belonging to various chemical classes and their activity, as well as selectivity towards the receptors, have been discussed in detail.

Conclusion: This review will help the researchers gain a fundamental understanding of TRKs, how this protein family works, and the ways to create chemical moieties, such as TRK inhibitors, which can serve as tailored therapies for cancer.

On the other hand, undergoing debulking surgery becomes challenging, and therapy with many chemotherapeutic medications has manifested resistance, a condition known as multidrug resistance (MDR). Although there are other therapeutic options for ovarian cancer, this article solely focuses on co-delivery techniques, which work via diverse pathways to overcome cancer cell resistance. Different pathways contribute to MDR development in ovarian cancer; however, usually, pump and non-pump mechanisms are involved. Striking cancerous cells from several angles is important to defeat MDR. Nanocarriers are known to bypass the drug efflux pump found on cellular membranes to hit the pump mechanism.

Nanocarriers aid in the treatment of ovarian cancer by enhancing the delivery of chemotherapeutic drugs to the tumour sites through passive or active targeting, thereby reducing unfavorable side effects on the healthy tissues. Additionally, the enhanced permeability and retention (EPR) mechanism boosts the bioavailability of the tumour site. To address the shortcomings of conventional delivery, the current review attempts to explain the current conventional treatment with special reference to passively and actively targeted drug delivery systems (DDSs) towards specific receptors developed to treat ovarian cancer. In conclusion, tailored nanocarriers would optimize medication delivery into the intracellular compartment before optimizing intra-tumour distribution. Other novel treatment possibilities for ovarian cancer include tumour vaccines, gene therapy, targeting epigenetic alteration, and biologically targeted compounds. These characteristics might enhance the therapeutic efficacy.

Methods: The chemical structures of novel cinnamoyl derivatives (3a-i and 4a-i) were confirmed by NMR and MS analyses. The physicochemical properties and evaluation of the ADME profile of 3a-i and 4a-i were performed by the preADMETlab2.0 web program. Cinnamoyl derivatives 3a-i and 4a-i were tested in vitro for their cytotoxicity against the human healthy fibroblast (HDFa) cells using an MTT cell viability assay. Derivatives with no toxicity on HDFa cells were tested both on human glioblastoma (U87MG) and neuroblastoma (SHSY- 5Y) cells, chosen as an experimental model of brain tumors. Cell death mechanisms were analyzed by performing flow cytometry analyses.

Results: Cinnamoyl derivatives 3a-i and 4a-i showed good physicochemical and ADME properties suggesting that these compounds could be developed as oral drugs endowed with a high capability to cross the blood-brain barrier. Compounds (E)-1-methoxy-4-(2-(phenylsulfonyl)vinyl)benzene (2c) and (E)-N-benzyl-N-(2- (cyclohexylamino)-2-oxoethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide (3e) did not show cytotoxicity on healthy human fibroblast cells up to 100 μg/mL. The most anticarcinogenic molecule, compound 3e, emerged as the most potent anticancer candidate in this study. Flow cytometry results showed that compound 3e (25 μg/mL) application resulted in nearly 86% and 84% cytotoxicity in the U87MG and the SHSY-5Y cell lines, respectively. Compound 2c (25 μg/mL) resulted in 81% and 82% cytotoxicity in the U87MG and the SHSY-5Y cell lines, respectively.

Conclusion: Cinnamoyl derivative 3e inhibits the proliferation of cultured U87MG and SHSY-5Y cells by inducing apoptosis. Further detailed research will be conducted to confirm these data in in vivo experimental animal models.

Objective: To determine whether ATO combined with ITRA can be used to treat NB with HH pathway activation, we examined the effects of ATO and ITRA monotherapy or combined inhibition of the HH pathway in NB.

Methods: Analysis of CCK8 and flow cytometry showed cell inhibition and cell cycle, respectively. Real-time PCR analysis was conducted to assess the mRNA expression of HH pathway.

Results: We revealed that as concentrations of ATO and ITRA increased, the killing effects of both agents on SK-N-BE(2) cells became more apparent. During G2/M, the cell cycle was largely arrested by ATO alone and combined with ITRA, and in the G0/G1 phase by ITRA alone. In the HH pathway, ATO inhibited the transcription of the SHH, PTCH1, SMO and GLI2 genes, however, ITRA did not. Instead of showing synergistic effects in a combined mode, ITRA decreased ATO inhibitory effects.

Conclusion: We showed that ATO is an important inhibitor of HH pathway but ITRA can weaken the inhibitory effect of ATO. This study provides an experimental evidence for the clinical use of ATO and ITRA in the treatment of NB with HH pathway activation in cytology.

Objectives: Current research focused on design of Tacrine-Flavone hybrids as multitargeted cholinesterase and monoamine oxidase B inhibitors.

Methods: A total of 10 Tacrine- Flavone hybrids were designed, synthesized and characterized. The in vitro neurotoxicity and hepatotoxicity of the synthesized compounds determined using SHSY5Y cell line and HEPG2 cell line. One most active compound (AF1) with least toxicity in in vitro studies was chosen for in vivo studies. Acute and subacute toxicity of the novel compound AF1 conducted on Wistar rats according to OECD guideline 423 and 407. The LD50 value of the novel compound calculated according to Finney’s method using Probit analysis. Anti-Alzheimer’s activity studies conducted on male Wistar rats. Behavioral studies conducted and AChE and MAO-B activity determined in rat brain.

Results and Discussion: All the compounds exhibited good inhibitory effect on MAO B and AChE. The neurotoxicity studies of the active compound AF1 did not show toxicity up to 100μg. The hepatotoxicity study of the most active compound AF1, showed the compound to be safe up to 200μg. The LD 50 value of the novel compound after a single oral administration was found to be 64 mg/kg bodyweight in rats. Subacute toxicity studies did not show any remarkable toxicity in the vital organs up to 40 mg/kg. Activity studies showed comparable results with standard at 20 mg/kg.

Conclusion: The results showed that the novel Tacrine-Flavone hybrids are multitarget-directed ligands, which are safe and active compared to tacrine and can be a promising lead molecule for further study.

Aim: The aim of this experimental synthesis was to generate potential treatment agents for Alzheimer's disease using serotonin conjugated with natural sesquiterpene lactones.

Methods: Three novel compounds were obtained via the Michael reaction and used for biological testing. The obtained conjugates demonstrated complex neuroprotective activities. Serotonin conjugated to isoalantolactone exhibited strong antioxidant and mitoprotective activities.

Results: The agent was also found to inhibit β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), prevent the aggregation of β-amyloid peptide 1-42, and protect SH-SY5Y neuroblastoma cells from neurotoxins such as glutamate and H₂O₂. In a transgenic animal model of Alzheimer's disease (5xFAD line), the conjugated agent restored declined cognitive functions and improved learning and memory.

Conclusion: In conclusion, the obtained results indicate that serotonin conjugates to sesquiterpene lactones are promising agents for the treatment of symptoms associated with Alzheimer's disease.

Objective: To study the antitumor activity of nanaomycin A against neuroblastoma cell lines and its mechanism.

Methods: The anti-tumor effect of nanaomycin A on neuroblastoma cell lines was evaluated based on cell viability, DNA methylation levels, apoptosis-related protein expression, and neuronal-associated mRNA expression.

Results: Nanaomycin A decreased genomic DNA methylation levels and induced apoptosis in human neuroblastoma cells. Nanaomycin A also upregulated the expression of mRNAs for several genes related to neuronal maturation.

Conclusions: Nanaomycin A is an effective therapeutic candidate for treating neuroblastoma. Our findings also suggest that the inhibition of DNA methylation is a promising anti-tumor therapy strategy for neuroblastoma.

Objectives: The aims of the current study are: 1) to summarize the advantages and dose-limiting effects of the approved and unapproved chemotherapy platinum cytostatics, 2) to develop new strategies for the development of platinum anticancer drugs, and 3) to clarify the important factors for the mechanism of action of platinum complexes.

Methods: A search was conducted in the literature databases, and the obtained information was summarized and analyzed.

Results: Myelosuppression is the main dose-limiting effect and the reason for the disapproval of platinum complexes, such as picoplatin, enloplatin, miboplatin, sebriplatin, zeniplatin, spiroplatin, iproplatin, and ormaplatin. From the basic point of view of inorganic coordination chemistry, such as theoretical calculations, crystal structures of model complexes, docking structures with nucleic acid molecules, spectroscopy, and biological aspects, the importance of physicochemical properties of inorganic platinum complexes for their mechanism of action has been indicated. Spectroscopic methods, such as FTIR, NMR, X-ray crystal structure analysis, and fluorescence microscopy, are important for the investigation of the conformational changes in the binding of platinum complexes and DNA.

Conclusion: In the development of platinum complexes, strong anti-cancer drug activity, low toxicity, and resistance can be obtained by the application of polynuclear platinum agents, complexes with targeted activity, and nanoparticle formulations. Electronic structure, stereochemical, and thermodynamic properties are essential for understanding the reaction mechanism of platinum complexes.

Materials and Methods: The RNA expression levels of lincRNA-p21, p53, p16, and telomere length were examined with reverse transcription-quantitative polymerase chain reaction (RTqPCR). The Telo TAGGG™ Telomerase PCR ELISA PLUS Kit was used to determine telomerase activity. Cellular viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) assay. Western blot was performed to analyze β-catenin protein expression. Besides, oxidative stress was evaluated by Jaggregate- forming delocalized lipophilic cation, 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolocarbocyanine++ + iodide (JC‑1) stain, fluorescence spectrophotometry, colorimetric assay, and malondialdehyde (MDA) formation.

Results: This research demonstrated that MPP⁺ caused a distinct increase in the expression of LincRNA- p21 in SH-SY5Y cells. MPP⁺ induced cellular senescence with decreasing cellular proliferation and viability, increasing expression levels of senescence-associated makers such as genes p53 and p16, accompanied by significantly decreasing telomere length and telomerase activity. At the same time, these effects were abolished by silencing lincRNA-p21 with small interfering RNA (siRNA). On the contrary, β-catenin silencing contributes to reversing anti-senescent effects caused by lincRNA-p21 silencing. Moreover, modifying lincRNA-p21 exerted an anti-senescent influence depending on decreasing oxidant stress.

Conclusion: Our study showed that in the treatment of MPP⁺, lincRNA-p21 might serve a role in the SH-SY5Y cell senescence by modulating the Wnt/β-catenin pathway, as well as increasing oxidant stress. Thus, trying to target lincRNA-p21 may have important therapeutic and practical implications for PD.

Methods: BCHE-deleted cells (KO) were produced from MYCN-amplified BE(2)-C cells (WT) by the CRISPR-Cas9 targeted disruption of the BCHE locus. Activation levels of several oncoproteins and the expression of N-Myc in KO were compared to WT cells. N-Myc protein expression, multiplexed detection of relative protein expression and phosphorylation of 71 tyrosine kinases and 17 proteins in the MAPK pathway were assessed using Western immunoblotting and microarrays in exponentially growing untreated cells and in cells exposed to the genotoxic stress.

Results: BCHE locus disruption and butyrylcholinesterase deficiency result in the loss of N-Myc protein and a significant deactivation of several kinases associated with the aggressive neuroblastoma phenotype as well as major changes in the phosphorylation of upstream and downstream partners of these kinases.

Conclusion: Butyrylcholinesterase appears to contribute to the activation of several pathways in MYCN-amplified cells including FGF-R1, Ltk, TrkB, and Ros1. Deletion of BCHE and ensuing butyrylcholinesterase deficit deactivate these pathways suggesting the role of BChE as a novel druggable target in neuroblastoma therapy.

Background: Dynamin plays a role in regulating neurotransmission, signaling pathways, nutrient uptake, and pathogen infection, enhancing cell proliferation, tumor invasion, and metastasis. Studies have reported that dyngo-4a, a dynamin inhibitor, can be used to identify potential biomarkers and promising novel therapeutic targets for cancer treatment.

Objective: To our knowledge, no published reports are showing that dynamin inhibitors can reduce NB cell proliferation and induce differentiation. In this study, we report that dyngo-4a can inhibit NB proliferation and induce NB cell differentiation.

Methods: In this study, mouse neuroblastoma (Neuro-2a) cells were cultured in the presence or absence of dyngo-4a or retinoic acid (RA), or in the presence of both dyngo-4a and RA, or in the presence of sequential administration of dyngo-4a and RA to compare the effects on the inhibition of cell proliferation and effects on neuroblastoma cell differentiation induction. The neural cell markers, Nestin and Tuj 1 (Neuron-specific class III beta-tubulin), were used to demonstrate that the differentiated cells have neuronal cell features. The phosphorylation of Protein Kinase B (AKT), extracellular signalregulated kinases1/2 (ERK1/2), and epidermal growth factor receptor (EGFR) were determined to examine the potential mechanisms of induced differentiation.

Results: Dyngo-4a or RA or dyngo-4a with subsequent RA administration induced Neuro-2a cell differentiation. However, RA with subsequent dyngo-4a administration results in almost total death of the Neuro-2a cells. The differentiation rate induced by dyngo-4a was significantly higher than the rate by RA treatment (72.5 ± 1.4% vs. 52.9 ± 3.1% with neuron features, P<0.05; 39.0 ± 0.8% vs. 29.9 ± 1.8% for axons under light microscopy, p<0.05). The differentiation rate of cells treated with dyngo-4a first, followed by RA, was greater than when they were added together (74.8 ± 3.8% vs. 10.6 ± 3.6%; 45.5 ± 1.6% vs. 12.4 ± 0.6%, p<0.01). Co-administration of dyngo-4a and RA at the same time diminished differentiation efficacy significantly. Dyngo-4a induced Neuro-2a cell differentiation and increased Tuj-1 positive staining by the 6^th day post- treatment. Dyngo-4a also inhibited Neuro-2a cell proliferation in a dose-dependent manner. Regarding the mechanism, dyngo-4a treatment showed a significant increase in p-AKT and p-ERK1/2 but not in p-EGFR.

Conclusion: At a level comparable to RA, dynamin inhibition with dyngo-4a lowers proliferation and causes differentiation of Neuro-2a mouse NB cells in vitro. The AKT pathway is activated by dynago- 4a, which results in differentiation. The combination of RA with dynago-4a reduces the efficiency of differentiation. The application of dynago-4a followed by RA, on the other hand, enhances the differentiating effect, implying alternative mechanistic roles in the process.

Objective: This work expounded on the function of Dex pretreatment in Sev-initiated neurotoxicity.

Methods: At first, human neuroblastoma cells (SK-N-SH cells) were treated with different concentrations of Sev or Dex, followed by the cell counting kit (CCK)-8 assay to decide the appropriate concentrations of Sev or Dex. Cell viability, lactate dehydrogenase (LDH) productions, and apoptotic rate of SK-N-SH cells were examined by the CCK-8 assay, LDH cytotoxicity kit, and flow cytometry assay in sequence. Further, reactive oxygen species (ROS) levels and proinflammatory cytokine contents were examined by the ROS assay kit and the enzyme-linked immunosorbent assay kits. The expression patterns of microRNA (miR)-204-5p and SRY-box transcription factor 4 (SOX4) in SK-N-SH cells were measured by real-time quantitative polymerase chain reaction or Western blotting. The binding relationship between miR-204-5p and SOX4 was confirmed by the dual-luciferase assay. After transfection of miR-204-5p mimics or SOX4 siRNA, the role of the miR-204-5p/SOX4 axis in Sev-initiated neurotoxicity was detected.

Results: Sev treatment reduced SK-N-SH cell viability in a concentration-dependent manner, and Dex pretreatment diminished Sev-initiated neurotoxicity. Mechanically, Dex pretreatment limited Sevinduced upregulation of miR-204-5p and further increased SOX4 expression levels. miR-204-5p upregulation or SOX4 knockdown averted the neuroprotection function of Dex pretreatment in Sevinitiated neurotoxicity.

Conclusion: Dex pretreatment decreased miR-204-5p expression levels and upregulated SOX4 expression levels, palliating Sev-initiated neurotoxicity.

We have a very limited understanding of this extremely complex topic, which is characterised by hypoxia- induced resistance. In order to combat this, scientists are investigating numerous cutting-edge approaches. Traditional chemotherapeutic drugs used to treat cancer are frequently linked to unfavourable side effects and the development of chemoresistance. The use of natural compounds in conjunction with chemotherapy drugs is rising as a result of their capacity to alter a number of molecular practices with a lower detrimental impact. Experimental and clinical research is accumulating evidence that phytochemicals can influence the genesis and progression of cancer by favourably modulating a number of signalling pathways. Combinations of phytochemicals are potent cancer treatment options because they incentivise apoptosis, limit cell prevalence, make cancerous cells more susceptible, and escalate immunity. Despite being characterised, HIF-1-independent mechanisms for medication resistance in hypoxia are still infrequently reported. The prime aim of the article is to summarise the most recent research on the molecular basis of hypoxia-induced chemoresistance and how chemotherapy and phytochemicals can be used to treat cancer patients who are resistant to drugs.

This review focuses on advancements in the field of natural and synthetic occurring piperidines active against Alzheimer’s disease, with emphasis on the past 6 years. The discussion also includes the structure-activity relationship, the structures of the most promising molecules, and their biological activities against Alzheimer’s disease. The promising activities revealed by these piperidinebased scaffolds undoubtedly place them at the forefront of discovering prospective drug candidates. Thus, it would be of great interest to researchers working on synthesizing neuroprotective drug candidates.

Methods: We propose a compilation and analysis of around 100 medications, including small new molecular entities (NMEs), approved by the US Food and Drug Administration for the years 2020 and 2021. Novel drug discovery is crucial for pharmaceutical research and development as well as patient care. The only possible way to achieve this crucial goal is to repurpose current medications that may have anticipated effects as possible candidates. The availability of new drugs and biological products often means new treatment options for patients and advances in health care.

Results: Around 40% of the drugs were approved for various types of cancers. Other major therapeutic areas that were focused on were neurological products (around 17%), infectious diseases (13-15%), and cardiovascular disorders (7-8%). Various new products were approved for rare diseases (58-60%). This study aimed to discover a pattern in FDA medicine approvals during the last two decades.

Conclusion: This data shows that anticancer medicines and biologics are receiving increased attention in research. With a bigger number of biologically derived medications being produced, the price could rise much higher. FDA should embrace innovative techniques that will stimulate the industry to enhance research and development of novel compounds or medications that can deliver considerable improvements over existing ones. To put it briefly, FDA had to update our approach to regulation as a whole in order to effectively develop the types of technologies that are becoming available. Modernizing medical product review programmes is a part of this. These initiatives are part of the Medical Innovation Access Plan.

Methods: Successive solvent extraction of A. precatorius leaves was carried out using the Soxhlet apparatus with solvents such as petroleum ether, chloroform, ethyl acetate, and ethanol. HPTLC fingerprinting and LC-MS studies were performed to assess the presence of secondary metabolites, such as flavonoids and phenols, in the ethyl acetate extract. Furthermore, the cytotoxic effect of extracts was tested on rat skeletal muscle cell line L6 and human neuroblastoma cell line SK-N-MC using MTT assay.

Results: The total phenolic content of ethyl acetate and ethanol extracts of A. precatorius were 72.67 and 60.73 mg, respectively, of GAE/g dry weight of the extract. The total flavonoid content of ethyl acetate and ethanol extract of A. precatorius were 107.33 and 40.66 mg of Quercetin equivalents/g dry weight of the extract. LCMS analysis demonstrated that the flavonoids in specific Naringenin, Diosmetin, Glycitin, and Genistein might play a prominent role in the cytotoxicity of A. precatorius. The cytotoxicity study revealed that the extracts of A. precatorius were non-toxic to rat L6 myotubes, and the IC₅₀ values of the various extracts, such as APPE, APCH, APEA, and APET, were >100 μg/ml. The extracts exhibited cytotoxic activity against human neuroblastoma SK-N-MC cells, and the IC₅₀ values of APPE, APCH, APEA, APET, and the standard drug “Cisplatin” were >100, >100, 64.88, >100, and 3.72 μg/ml, respectively.

Conclusion: It was concluded from the study that the extracts of Abrus precatorius were cytotoxic to neuroblastoma cell lines but non-toxic to normal cell lines. HPTLC and LC-MS studies confirmed that flavonoids in the ethyl acetate extract could be responsible for the biological activity.

Objectives: The aim of this work is to obtain new peptide derivatives of 4-aminopyridine with decreased toxicity compared to 4-aminopyridine.

Methods: Synthesis was conducted in solution using a consecutive condensation approach. The new derivatives were characterized by melting points, NMR, and Mass spectra. Important ADME (absorption, distribution, metabolism, and excretion) properties have been studied in silico using ACD/Percepta v.2020.2.0 software. Acute toxicity was determined in mice according to a Standard protocol. All new derivatives were tested in vitro for cytotoxic activity in a panel of human (HEP-G2, BV-173) and murine (NEURO 2A) tumor cell lines via a standard MTT-based colorimetric method. β-secretase inhibitory activity was determined by applying the fluorescent method.

Results: New derivatives of 4-aminopyridine containing analogues of the β-secretase inhibitory peptide (Boc-Val-Asn-Leu-Ala-OH) were obtained. The in vivo toxicity of the tested compounds was found to be as high as 1500 mg/kg. Cell toxicity screening against tumor cell lines of different origins showed negligible growth-inhibitory effects of all investigated 4-aminopyridine analogues.

Conclusion: Synthesis of new peptide derivatives of 4-aminopyridine is reported. Acute toxicity studies revealed a ca. 150 times lower toxicity of the new compounds as compared to 4-aminopyridine that may be ascribed to their peptide fragment.

Objective: To analyze pathophysiological characteristics/co-morbidities precipitating myocardial ischemia in patients with HTN LVH and provide a rationale for recommending beta-blockers (BBs) to prevent/treat ischemia in LVH.

Methods: We searched PubMed, SCOPUS, PubMed, Elsevier, Springer Verlag, and Google Scholar for review articles and guidelines on hypertension from 01/01/2000 until 01/05/2022. The search was limited to publications written in English.

Results: HTN LVH worsens ischemia in coronary artery disease (CAD) patients. Even without obstructive CAD, several pathophysiological mechanisms in HTN LVH can lead to myocardial ischemia. In the same guidelines that recommend BBs for patients with HTN and CAD, we could not find a single recommendation for BBs in patients with HTN LVH but without proven CAD. There are several reasons for the proposal of using some BBs to control ischemia in patients with HTN and LVH (even in the absence of obstructive CAD).

Conclusion: Some BBs ought to be considered to prevent/treat ischemia in patients with HTN LVH (even in the absence of obstructive CAD). Furthermore, LVH and ischemic events are important causes of ventricular tachycardia, ventricular fibrillation, and sudden cardiac death; these events are another reason for recommending certain BBs for HTN LVH.

Methods: YF-343 was estimated as a novel HDACi by the HDACi drug screening kit. The biological effects of YF-343 in a panel of breast cancer cell lines were analyzed by Western blot and flow cytometry. YF-343 exhibited notable cytotoxicity, promoted apoptosis, and induced cell cycle arrest. Furthermore, it also induced autophagy, which plays a pro-survival role in breast cancer cells.

Results: The combination of YF-343 with an autophagy inhibitor chloroquine (CQ) significantly suppressed breast tumor progression as compared to the YF-343 treatment alone both in vitro and in vivo. Mechanistically, the molecular mechanism of YF-343 on autophagy was elucidated by gene chip expression profiles, qPCR analysis, luciferase reporter gene assay, chromatin immunoprecipitation assays, immunohistochemical analysis, and other methods. E2F7, a transcription factor, promoted the expression of ATG2A via binding to the ATG2A promoter region and then induced autophagy in triple-negative breast cancer cells treated with YF-343.

Conclusion: Our studies have illustrated the mechanisms for potential action of YF-343 on tumor growth in breast cancer models with pro-survival autophagy. The combination therapy of YF-343 and CQ maybe a promising strategy for breast cancer therapy.

Methods: We have reviewed PubMed and EMBASE libraries to gather data on the mechanism-based pharmacological management of chemotherapy-induced neuropathic pain.

Results: This review has focused on the potential mechanisms by which these chemotherapeutic agents may be involved in the development of CIPN, and explains how this may be translated into clinical management. Additionally, we have presented an overview of emerging candidates for the prevention and treatment of CIPN in preclinical and clinical studies.

Conclusion: Taken together, due to the debilitating consequences of CIPN for the quality of life and clinical outcome of cancer survivors, future studies should focus on identifying underlying mechanisms contributing to CIPN as well as developing effective pharmacological interventions based on these mechanistic insights.

Methods: The contents of the present review were based on information obtained from PubMed. In the data search, “NR2F1-AS1” was chosen as the first keyword, whereas “cancer” was chosen as the second keyword. This review selected and summarized studies published between 2019-2021, concerning the biological functions and mechanisms of NR2F1-AS1 in the development of tumorigenesis.

Results: It was found that NR2F1-AS1 regulates a variety of biological activities such as proliferation, invasion, migration, and apoptosis. It acts as an oncogene because it is abnormally expressed and promotes the progression of cancer in a variety of malignancies, including esophageal squamous cell carcinoma, non-small cell lung cancer, breast cancer, neuroblastoma, endometrial cancer, thyroid cancer, and gastric cancer. However, it was evident that NR2F1-AS1 inhibits the progression of cancer in cervical squamous cell carcinoma.

Conclusion: NR2F1-AS1 is a potential new biomarker and therapeutic target for the treatment of different cancers.

Objective: The aim of the study is to investigate the anticancer effect of erianin and the underlying mechanism of this effect on SH-SY5Y cells.

Methods: The effects of erianin on cell viability, invasion and migration were determined by XTT, matrigel chamber and wound healing evaluation, respectively. Expression changes of miRNAs (microRNA) and apoptosis-related genes were evaluated by RT-PCR, and the apoptosis rate was supported by Annexin V evaluation.

Results: Erianin significantly decreased cell proliferation, invasion and migration. Erianin administration caused apoptosis by significantly increasing caspase-7, FADD (Fas-associated protein with death domain), BID (BH3 Interacting Domain Death Agonist) and DR5 (Death receptor 5) gene expressions. While the rate of total apoptotic cells was 45.35 ± 6.80% in SH-SY5Y cells treated with erianin, it was 0.133 ± 0.05% in the control group (p = 0.000). In addition, erianin administration significantly decreased the expressions of hsa-miR-155-5p (p = 0.014) and hsa-miR-223-3p (p = 0.004). Also, our study demonstrated for the first time the relationship between erianin and mi-RNAs in a cancer cell.

Conclusion: Our study suggests that erianin may be a natural, safe and easily accessible drug candidate that can be used in the treatment of neuroblastoma.

Background: Dihydropyridines constitute an important class of calcium channel blockers (CCBs) due to their high potency, wide heterogeneity and tremendous biological usefulness. As a follow-up to our previous studies on 4-aryl-1,4-dihydropyridines as calcium channel blockers for the treatment of hypertension, four new series of methyl ethyl ester substituted 1,4-dihydropyridines are reported.

Objectives: The aim of the work was to study the effects of unsymmetrical ester substitutions on calcium channel blocking activity of dihydropyridines (DHPs) while retaining the aminoalkoxy side chain at various positions of the 4-aryl ring. The type and location of the substituents on the 4-aryl ring have been extensively explored to study the structure-activity relationship (SAR) in this series of dihydropyridines as calcium channel blockers.

Methodology: The target DHPs were synthesized using modified Hantzsch condensation and further derivatization. The compounds were screened for their inhibitory potential against L-type calcium channels at a single concentration of 10 μM on NG108-15 cells (Neuroblastoma X Glioma). The most potent DHP 12 was also tested for its vasodilatory activity using rat thoracic aortic rings precontracted with KCl (30 mM) and in vivo antihypertensive activity in rats using the tail-cuff method.

Results: The newly synthesized DHPs displayed diversified calcium channel blocking activity with compounds 1e, 1h, 2d, 2f, 2h, 6, 9, 11, 12 and 14, producing more than 50% inhibition of veratridine response. 3-imidazolylpropoxy substituted analogue 12 turned out to be the most potent compound of the four series of compounds and produced fairly higher inhibition (78.6%) of veratridine response in comparison to nifedipine (70%) at 10 μM. In addition, compound 12 produced potent vasodilatory and antihypertensive properties.

Conclusion: Both location of the side chain and the type of substituent on methyl ethyl ester substituted 4-aryl ring affected the response of dihydropyridine derivatives towards L-type calcium channels.